(Press-News.org) Senescent cells have a bad-guy reputation when it comes to aging. While cellular senescence - a process whereby cells permanently lose the ability to divide when they are stressed - suppresses cancer by halting the growth of premalignant cells, it is also suspected of driving the aging process. Senescent cells, which accumulate over time, release a continual cascade of inflammatory cytokines, chemokines, growth factors and proteases. It is a process that sets up the surrounding tissue for a host of maladies including arthritis, atherosclerosis and late life cancer. But in a study publishing online in advance of the December 22nd edition of Developmental Cell, Buck Institute faculty Judith Campisi, PhD, postdoctoral fellow Marco Demaria, PhD and colleagues show that senescent cells act as good-guys when it comes to wound healing. Moreover, they identified a single factor secreted by senescent cells that cause them to promote wound healing. It's a crucial discovery for researchers (including Campisi) who are working on developing treatments to clear the body of senescent cells as a way to stem the development of age-related disease.
"What is most exciting is that we are now able to identify what senescent cells express that makes them beneficial," said Campisi, senior scientist on the study. "This means we will be able to simply provide that factor while we eliminate senescent cells to prevent a deleterious side effect before it even occurs."
Postdoctoral fellow, Marco Demaria, PhD, lead author of the study, used two different mouse models: in the first, which was developed in collaboration with colleagues at the Erasmus, Harvard and Einstein Medical Schools, senescent cells can be visualized and eliminated in living animals; in the second, which was developed by Eiji Hara, Naoko Ohtani and colleagues at the Japanese Foundation for Cancer Research, mutations in two key genes block the senescence program. Demario showed that following a skin wound, senescence occurs early on in cells that produce collagen and line blood vessels. Demaria said the senescent cells accelerated wound closure through the secretion of PDGF-AA, a growth factor contained within blood platelets, making it the "good guy" in this portrayal of senescence. "We were able to apply recombinant PDGF-AA topically to mice that had senescent-free wounds," said Demaria. "It rescued delayed wound closure and allowed the mice to heal normally."
The researchers also found that senescent cells were present only for a short time during tissue repair, in contrast to the persistent presence of senescent cells in aged or chronically damaged tissues. Moreover, they say the fact that PDGF-AA was activated very early upon senescence induction in cell culture suggests the time-dependent regulation of secretory factors might, in part, explain the beneficial vs. deleterious effects of senescent cells.
Campisi says the finding shows that, in addition to preventing cancer in the young, cellular senescence might play a beneficial role in human health, perhaps throughout the entire lifespan. "It is essential that we understand the full impact of senescence," Campisi said. "The possibility of eliminating senescent cells holds great promise and is one of the most exciting avenues currently being explored in efforts to extend healthspan. This study shows that we can likely harness the positive aspects of senescence to ensure that future treatments truly do no harm." The researchers now plan to explore the role of senescent cells in other examples of tissue injury.
INFORMATION:
This work was supported by grants from the American Italian Cancer Foundation, the Japan Science and Technology Agency, the US National Institutes of Health (AG017242, AG009909 and AG041122), and a European Council Advanced Grant. The authors declare no conflicts of interests.
Other contributors include: Francis Rodier and Remi-Martin Laberge from the Buck Institute; Naoko Ohtani and Eiji Hara, Division of Cancer Biology, The Japanese Foundation for Cancer Research, Koto-ku, Tokyo; Sameh A. Youssef and Alain de Bruin, Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands; Wendy Toussaint, James R. Mitchell and Jan H. J. Hoeijmakers, CGS Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands; Jan Vijg, Department of Genetics, Albert Einstein College of Medicine, Bronx, NY; Harry Van Steeg, Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands; Martijn E. T. Dollė, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
About the Buck Institute for Research on Aging
The Buck Institute is the U.S.'s first independent research organization devoted to Geroscience - focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending "Healthspan", the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org
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"One implication is that world religions and secular spiritualities ...
EMBARGOED for release Thursday, Dec. 11, 2014, at 12 p.m. ET
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Appearing online ...
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"We know ...
The saga of the Osedax "bone-eating" worms began 12 years ago, with the first discovery of these deep-sea creatures that feast on the bones of dead animals. The Osedax story grew even stranger when researchers found that the large female worms contained harems of tiny dwarf males.
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